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We examined whether tau-PET subtype modified the association between plasma p-tau217 and memory.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>\n                    We analyzed 396 amyloid-positive, tau-positive participants spanning cognitively unimpaired, mild cognitive impairment, and dementia stages from six cohorts with tau-PET and plasma p-tau217; 301 had harmonized memory data. Tau-PET subtypes were derived using data-driven disease progression modelling. Primary cross-sectional models tested subtype\u00d7p-tau217 interactions for memory, adjusting for age, sex, education,\n                    <jats:italic>APOE<\/jats:italic>\n                    \u03b5\n                    <jats:italic>4<\/jats:italic>\n                    status, and cohort. Secondary and exploratory analyses examined latent global cognition, non-memory measures, and longitudinal cognitive change.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>\n                    Three tau-PET subtypes were retained: limbic-predominant, medial temporal lobe (MTL)-sparing, and posterior-predominant. Cross-sectionally, MTL-sparing participants had lower plasma p-tau217 than the other subtypes. The association between higher plasma p-tau217 and worse memory differed by subtype (interaction\n                    <jats:italic>p<\/jats:italic>\n                    =0.002) and was stronger in MTL-sparing (\n                    <jats:italic>B<\/jats:italic>\n                    =-0.191,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.001) than in limbic-predominant (\n                    <jats:italic>B<\/jats:italic>\n                    =-0.07,\n                    <jats:italic>p<\/jats:italic>\n                    =0.002) and posterior-predominant participants (\n                    <jats:italic>B<\/jats:italic>\n                    =-0.07,\n                    <jats:italic>p<\/jats:italic>\n                    &lt;0.001). The interaction remained significant after additional adjustment for diagnostic group (\n                    <jats:italic>p<\/jats:italic>\n                    =0.015). This pattern also persisted after additional adjustment for PET tau burden, amyloid Centiloids, or plasma A\u03b242\/40; none of these biomarkers showed comparable subtype modification. Subtype modification was also observed for a global cognitive composite (interaction\n                    <jats:italic>p<\/jats:italic>\n                    =0.004) and subsequent memory decline in an exploratory analysis conditioned on baseline memory (interaction\n                    <jats:italic>p<\/jats:italic>\n                    =0.016).\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>DISCUSSION<\/jats:title>\n                  <jats:p>Tau-PET subtype modified the p-tau217\u2013memory association, suggesting that the cognitive implications of plasma p-tau217 may vary with tau topography.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.25.26363629","type":"posted-content","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:55:12Z","timestamp":1790628912000},"source":"Crossref","is-referenced-by-count":0,"title":["Tau-PET subtype modifies the association between plasma p-tau217 and memory in Alzheimer\u2019s disease"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1328-2791","authenticated-orcid":false,"given":"Lukai","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1733-9928","authenticated-orcid":false,"given":"Elham","family":"Ghanbarian","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1173-7329","authenticated-orcid":false,"given":"Carlos","family":"Albarr\u00e1n Morillo","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Center for Design, Discovery, and Data Analytics (3D Center) in Neurological Disorders, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9912-1616","authenticated-orcid":false,"given":"Kyan","family":"Younes","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1430-7463","authenticated-orcid":false,"given":"Crystal M.","family":"Glover","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of California, Irvine, CA, USA"},{"name":"Alzheimer\u2019s Disease Research Center, Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8898-1514","authenticated-orcid":false,"given":"Laura A.","family":"Rabin","sequence":"additional","affiliation":[{"name":"The City University of New York, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4215-7589","authenticated-orcid":false,"given":"Joshua D.","family":"Grill","sequence":"additional","affiliation":[{"name":"Alzheimer\u2019s Disease Research Center, Institute for Memory Impairments and Neurological Disorders (UCI MIND), University of California, Irvine, CA, USA"},{"name":"Department of Psychiatry and Human Behavior, University of California, Irvine, CA, USA"},{"name":"Department of Neurobiology and Behavior, University of California, Irvine, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5231-1714","authenticated-orcid":false,"given":"Michael","family":"Ewers","sequence":"additional","affiliation":[{"name":"Institute for Stroke and Dementia Research, University Hospital, Ludwig Maximilian University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8960-2213","authenticated-orcid":false,"given":"S. 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